Sarah E. Blutt, Ph.D.
Department of Molecular Virology & Microbiology
Intestinal B Cell Responses To Enteric PathogensWith over 400 m2 of surface area and under continuous antigenic challenge, the intestine is a vulnerable port of entry into the body utilized by many pathogens. Within the complex immune system that is designed to prevent entry of pathogens at the intestinal surface lies over 80% of the activated B cells that are present in the human system. These B cells produce 40-60 mg/kg of IgA daily; more than any other isotype in the body. Although a major presence in the intestinal immune system, little is known about how intestinal B cells are activated and what signaling pathways regulate their differentiation and class-switching to IgA in response to pathogenic encounter. The focus of our research program is on investigating the B cell response to rotavirus, a major viral pathogen that causes severe diarrhea and results in over 600,000 deaths of children annually. Protection from rotavirus infection has been demonstrated to correlate with intestinal IgA suggesting that intestinal B cells play a significant role in immunity to rotavirus infection. There have been several unsuccessful attempts to develop a vaccine to prevent rotavirus disease and the long term goal of our program is to improve the understanding of intestinal immune responses and apply this understanding to better develop vaccines against enteric pathogens.
Currently, we are focused on understanding how rotavirus induces intestinal B cell activation and IgA production. Using a mouse model of rotavirus infection, we are investigating the role of rotavirus induced T-cell independent B cell activation that is mediated by non-classical pathways that involve dendritic cells, TNF, and the toll-like receptors. We are also investigating the role of the Peyer’s patches, specialized intestinal immune tissue that is comprised predominately of B cells, in rotavirus immunity. Additional work is focused on understanding the role that viral replication plays in immunity by comparing the immune responses induced by replicating virus to that induced by inactivated virus and virus-like particles. These studies will provide critical information on intestinal immunity within the B cell compartment that will be applied to oral vaccine design.
Baylor College of Medicine
One Baylor Plaza
Houston, TX 77030
Ph.D., Baylor College of Medicine
Postdoctoral, Baylor College of Medicine
Blutt, S.E., Kirkwood, C.D., Parreno, V., Warfield, K.L., Ciarlet, M., Estes, M.K., Bok, K., Bishop, R.F., Conner, M.E. Rotavirus Viremia: A Common Event? Lancet. 362:1445-1449. 2003.
Blutt, S.E., Warfield, K.L., O’Neal, C.M., Estes, M.K., Conner, M.E. Host, Viral, and Vaccine Factors that Determine Protective Efficacy Induced by Rotavirus and Virus-Like Particles (VLPs). Vaccine. 24:1170-1179. 2006.
Blutt, S.E., Fenaux, M., Warfield, K.L., Greenberg, H.B., Conner, M.E. Active Viremia in Rotavirus-Infected Mice. Journal of Virology. 80:6702-6705. 2006.
Warfield, K.L., Blutt, S.E., Crawford, S.E., Kang, G., Conner, M.E. Rotavirus Infection Enhances Lipopolysaccharide-induced Intussusception in a Mouse Model. Journal of Virology. 80:12377-12386. 2006.
Blutt, S.E., Matson, D.O. Crawford, S.E., Staat, M.A., Azimi, P., Bennett, B.L., Peidra, P.A., Conner, M.E. Rotavirus antigenemia in children is associated with viremia, PLoS Medicine. 4:e121. 2007
Blutt, S.E. and Conner, M.E. Rotavirus: To the Gut and Beyond! Current Opinions in Gastroenterology. 23:39-43. 2007